metabolic pathways

1. To understand what a metabolic pathway is and to know the terminology used to describe its components.

2. To appreciate the difference between anabolic and catabolic pathways.

3. To understand how free energy is exchanged between anabolic and catabolic pathways.

4. To learn the basic mechanisms for regulation of metabolic pathways.

5. To understand the role of ATP as a universal molecular free-energy currency.

Classes of metabolism

Single vs multistep pathways

• uncontrolled oxidation would have a single release of free energy

• total energy obtained from either single or multistep

• multistep pathway allows small regular amounts of energy to be released in some steps

  • cells can then use this free energy to synthesise atp for example

• in multistep:

  • each reaction uses one enzyme

  • reactions take place inside specific organelles in eukaryotic cells

  • regulated by key enzymes that can be activated or inhibited

Characteristics

• highly regulated

  • allow response to environmental changes

  • avoids futile cycles

• flow of material

  • depends on: supply of substrates, removal of products, pathway enzyme activities

Mechanism of regulation

Feedback inhibition

• committed step is specific to a reaction pathway

• common

Feed-forward activation

• inc levels of an intermediate can accelerate an enzyme further downstream

  • whole reaction becomes accelerated

Inhibition or activation from other pathways

• depends on energy, flux of substrates

• can control whole metabolism of the cell

Modulation of individual regulatory enzymes

• enzyme activity can be rapidly and reversibly altered by covalent modification

  • eg protein phosphorylation

  • adding or removing a group

• protein kinase phosphorylate enzymes via ATP

• protein phosphatases remove phosphate groups that have been previously added by kinases

Thermodynamics of metabolism

• if delta g is less than 0 the reaction is spontaneous, exergenic

• if delta g is more than 0 the reaction is endergonic, non-spontaneous

  • free energy required

• delta h less than 0 is exothermic

• delta h more than 0 is endothermic

Coupled reactions

• enzyme catalysed reactions are the sum of the endergonic and the exergonic reactions

  • amount of free energy released by exergonic is higher than required by endergonic

• two domains of hexokinase clamp down on the bound molecule of glucose and keep water out of the active centre

• when glucose and ATP bind to the active site of hexokinase the two substrates are in the correct orientation for phosphate transfer

Energy capture and transfer

Autotrophic and heterotrophic organisms use anabolism and catabolism

Anabolism

• minerals, amino acids, light energy (all used to make biopolymers such as carbs, proteins and fats

Catabolism is when these biopolymers are broken down to release the monomers and energy

• energy is used for movement, transport and cellular work

ATP

• all living organisms use atp for transferring free energy between reactions

• some processes with a large delta G<0 are used to drive synthesis of ATP (catabolic)

• hydrolysis of ATP can be used to drive biosynthetic pathways with delta G > 0 (anabolic)

Molecular structure

• adenosine = adenine + ribose

• triphosphate (overall charge of -4)

• magnesium - (makes overall charge -2)

→ specialised nucleotide

• 2 phosphate groups bound and released water

• adding back the water, hydrolysis, generates large amounts of free energy

• alpha phosphate is directly attached, then beta then gamma

• atp and adp hydrolysis release more free energy than amp